A necessary function of the intestinal epithelium is the establishment of a selective barrier to allow the absorption of nutrients while restricting the uptake of toxic substances and microbes from the gut lumen. A major component of this epithelial barrier is the tight junction (TJ), a circumferential protein complex located at the apical/basolateral junction of opposing cells. The TJ complex is believed to be the point of cell-cell contact that presents the major barrier to paracellular transport5,6.
Intestinal epithelial barrier function is compromised in a variety of inflammatory conditions including inflammatory bowel disease, cholestasis, hemorrhagic shock, and sepsis7. Many mechanisms, including activation of myosin light chain kinase and excessive nitric oxide (NO.) synthesis, have been proposed to explain the increase in paracellular permeability of intestinal epithelia following exposure to an inflammatory environment8,9. However, effective treatments are not available. Therefore, it would be advantageous to discover new pharmacological agents that are effective in preventing or treating a broad variety of inflammatory conditions, including compromised barrier function.